We, and others, have recently reported that GDNF or BMP7 protects against ischemia-induced injury in the cerebral cortex of adult rats. Since these trophic factors are highly expressed in the fetal, but not adult, kidney cortex, we examined the possibility that transplantation of fetal kidney tissue could serve as a cellular reservoir for such molecules and protect against ischemic injury in cerebral cortex. Fetal kidneys, obtained from rat embryos at gestational day 16, and adult kidney cortex, were dissected and cut into small pieces. Adult male Sprague-Dawley rats were anesthetized with chloral hydrate and placed in a stereotactic apparatus. Kidney tissues were transplanted into 3 cortical areas adjacent to the right middle cerebral artery (MCA). Thirty minutes after grafting, the right MCA was transiently ligated for 60 min. Seventy-two hours after the onset of reperfusion, animals were evaluated behaviorally. As examined by an Accuscan infra-red activity box, we found that the stroke animals receiving fetal kidney tissue transplantation manifested more locomotor activity compared to animals that received adult kidney tissue transplants. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride (TTC) staining and caspase-3 immunostaining. We found that transplantation of fetal kidney, but not adult kidney, tissue greatly reduced the volume of infarction in the cerebral cortex. Fetal kidney grafts showed less caspase-3 immunoreactivity in the host cerebral cortex. In contrast, caspase-3 was found in the adult kidney grafts and in the ischemic cortex. Taken together, our data indicate that fetal kidney transplantation reduces ischemia/reperfusion -induced cortical infarction and behavioral deficits in adult rats, possibly through the inhibition of caspase-3 -induced apoptosis expression in the ischemic brain.